G-protein coupled receptor nucleic acids, polypeptides, antibodies and uses thereof

Abstract

The invention provides isolated HGPRBMY1 and HGPRBMY2 nucleic acid molecules and polypeptide molecules. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule consisting of a polynucleotide having a nucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide encoding a polypeptide of SEQ ID NO:2;    (b) an isolated polynucleotide consisting of nucleotides 250 to 1323 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino cids 2 to 359 of SEQ ID NO:2 minus the start codon;    (c) an isolated polynucleotide consisting of nucleotides 247 to 1323 of SEQ ID NO:1, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 329 of SEQ ID NO:2 including the start codon;    (d) a polynucleotide encoding the HGPRBMY1 polypeptide encoded by the cDNA clone contained in ATCC Deposit No. XXXXX;    (e) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:1;    (a) a polynucleotide encoding a polypeptide of SEQ ID NO:14;    (b) an isolated polynucleotide consisting of nucleotides 362 to 1651 of SEQ ID NO:13, wherein said nucleotides encode a polypeptide corresponding to amino acids 2 to 431 of SEQ ID NO:14 minus the start codon;    (c) an isolated polynucleotide consisting of nucleotides 359 to 1651 of SEQ ID NO:13, wherein said nucleotides encode a polypeptide corresponding to amino acids 1 to 431 of SEQ ID NO:13 including the start codon;    (d) a polynucleotide encoding the HGPRBMY2 polypeptide encoded by the cDNA clone contained in ATCC Deposit No. XXXXX; and    (e) a polynucleotide which represents the complimentary sequence (antisense) of SEQ ID NO:13.    
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein the polynucleotide comprises a nucleotide sequence encoding a human G-protein coupled receptor protein.  
     
     
         3 . A recombinant vector comprising the isolated nucleic acid molecule of  claim 2 .  
     
     
         4 . A recombinant host cell comprising the recombinant vector of  claim 3 .  
     
     
         5 . An isolated polypeptide consisting of an amino acid sequence selected from the group consisting of: 
 (a) a full length protein of SEQ ID NO:2;    (b) a polypeptide corresponding to amino acids 2 to 359 of SEQ ID NO:2, wherein said amino acids 2 to 359 comprise a polypeptide of SEQ ID NO:2 minus the start methionine;    (c) a polypeptide corresponding to amino acids 1 to 359 of SEQ ID NO:2;    (d) a polypeptide encoded by the cDNA contained in ATCC Deposit No. XXXXX;    (e) a full length protein of SEQ ID NO:14;    (f) a polypeptide corresponding to amino acids 2 to 431 of SEQ ID NO:14, wherein said amino acids 2 to 431 comprise a polypeptide of SEQ ID NO:14 minus the start methionine;    (g) a polypeptide corresponding to amino acids 1 to 431 of SEQ ID NO:14; and    (h) a polypeptide encoded by the cDNA contained in ATCC Deposit No. XXXXX.    
     
     
         6 . A cell comprising the polypeptide of  claim 4  and a member selected from the group consisting of NFAT/CRE, and NFAT G alpha 15.  
     
     
         7 . A method of screening for candidate compounds capable of modulating activity of a G-protein coupled receptor-encoding polypeptide, comprising: 
 (a) contacting a test compound with the cell according to  claim 6;  and    (b) selecting as candidate modulating compounds those test compounds that modulate activity of the G-protein coupled receptor polypeptide.    
     
     
         8 . A polypeptide that binds to the polypeptide of  claim 1  selected from the group consisting of SEQ Id NO:32, 33, 34, and 35.  
     
     
         9 . The polypeptide of  claim 8  wherein said polypeptide modulates the G-protein coupled receptor of  claim 5 .  
     
     
         10 . A method of screening for candidate compounds capable of modulating activity of a G-protein coupled receptor-encoding polypeptide, comprising: 
 (a). contacting the modulating polypeptide of  claim 9  with the cell according to  claim 4;     (b). contacting a test compound with said cell; and    (c). selecting as candidate modulating compounds those test compounds that modulate activity of the G-protein coupled receptor polypeptide.    
     
     
         11 . A method of modulating the G-protein coupled receptor activity of the polypeptide of  claim 5  comprising an effective amount of the polypeptide of  claim 9 .  
     
     
         12 . The method for the treatment of immune-related disorders comprising a member of the group consisting of: 
 (a) administering to the subject a therapeutically effective amount of a HGPRBMY1 polypeptide;    (b) modulating the activity of a HGPRBMY1 polypeptide;    (c) administering to the subject a therapeutically effective amount of a HGPRBMY1 polypeptide wherein the HGPRBMY1 polypeptide is contained in a pharmaceutical composition;    (d) modulating the activity of a HGPRBMY1 polypeptide wherein the HGPRBMY1 polypeptide is HGPRBMY1 or a functionally equivalent derivative thereof;    (e) wherein the HGPRBMY1 polypeptide is HGPRBMY1 or a functionally equivalent derivative thereof wherein the HGPRBMY1 polypeptide is HGPRBMY1 or a functionally equivalent derivative thereof wherein the method comprises administering an effective amount of a compound that agonizes or antagonizes the activity of the HGPRBMY1 polypeptide;    (f) administering an effective amount of a compound that decreases expression of a HGPRBMY1 gene;    (g) administering an effective amount of a compound that decreases expression of a HGPRBMY1 gene in which the compound is an oligonucleotide encoding an antisense or ribozyme molecule that targets HGPRBMY1 transcripts and inhibits translation; and    (h) administering an effective amount of a compound that increases expression of a HGPRBMY1 gene.    
     
     
         13 . The method for the treatment of heart-related disorders comprising a member of the group consisting of: 
 (i) administering to the subject a therapeutically effective amount of a HGPRBMY2 polypeptide;    (j) modulating the activity of a HGPRBMY2 polypeptide;    (k) administering to the subject a therapeutically effective amount of a HGPRBMY2 polypeptide wherein the HGPRBMY2 polypeptide is contained in a pharmaceutical composition;    (l) modulating the activity of a HGPRBMY2 polypeptide wherein the HGPRBMY2 polypeptide is HGPRBMY2 or a functionally equivalent derivative thereof;    (m) wherein the HGPRBMY2 polypeptide is HGPRBMY2 or a functionally equivalent derivative thereof wherein the HGPRBMY2 polypeptide is HGPRBMY2 or a functionally equivalent derivative thereof wherein the method comprises administering an effective amount of a compound that agonizes or antagonizes the activity of the HGPRBMY2 polypeptide;    (n) administering an effective amount of a compound that decreases expression of a HGPRBMY2 gene;    (o) administering an effective amount of a compound that decreases expression of a HGPRBMY2 gene in which the compound is an oligonucleotide encoding an antisense or ribozyme molecule that targets HGPRBMY2 transcripts and inhibits translation; and    (p) administering an effective amount of a compound that increases expression of a HGPRBMY2 gene.    
     
     
         14 . A method for preventing, treating, or ameliorating a medical condition, comprising the step of administering to a mammalian subject a therapeutically effective amount of a member of the group consisting of: 
 (a) a polynucleotide of  claim 1;     (b) a polypeptide of  claim 5;     (c) an antagonist of the polypeptide of  claim 5;     (d) an agonist of the polypeptide of  claim 5;     (e) an antagonist of the polynucleotide of  claim 1;     (f) a agonist of the polynucleotide of  claim 1;     (g) the modulatory polypeptide of  claim 9;  and    (h) an antibody directed against the polypeptide of  claim 5 .    
     
     
         15 . The method of preventing, treating, or ameliorating a medical condition of  claim 14 , wherein the medical condition is selected from the group consisting of an immune disorder, a hematopoietic disorder, a pulmonary disorder, and a gastrointestinal disorder.  
     
     
         16 . The method of preventing, treating, or ameliorating a medical condition of  claim 14 , wherein the medical condition is selected from the group consisting of a cardiovascular disorder, a neural disorder, and a reproductive disorder.  
     
     
         17 . The method of preventing, treating, or ameliorating a medical condition of  claim 14 , wherein the medical condition is a cell cycle defect, a disorder related to aberrant phosphorylation, a disorder related to aberrant signal transduction, a proliferating disorder, an autoimmune disorder, a disorder related to hyper immune activity, an inflammatory condition, a disorder related to aberrant acute phase responses, a hypercongenital condition, a birth defect, a necrotic lesion, a wound, organ transplant rejection, and a condition related to organ transplant rejection.  
     
     
         18 . The method of preventing, treating, or ameliorating a medical condition of  claim 14 , wherein the medical condition is a metabolic disorder, obesity, and pain.  
     
     
         19 . The method of preventing, treating, or ameliorating a medical condition of  claim 14 , wherein the condition is a condition related to aberrant cell cycle regulation, aberrant p27 regulation, aberrant apoptosis regulation, aberrant IkB regulation, aberrant NFkB regulation, aberrant DNA repair, and aberrant cellular phophorylation.  
     
     
         20 . The isolated polypeptide of  claim 5 , wherein the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.